Proteoglycan aggregates are major structural constituents of cartilage extracellular matrix. They are believed to be inhibitory of mineralization. They are removed and replaced in bone, as in dentin, by smaller non-aggregative proteoglycans with different and possibly specific functions. With a view to aiding studies of the initiation of mineralization, we propose to extend our work on cartilage proteoglycan structure and interactions. We have reported on the complete primary sequence of link protein and the hyaluronate binding region of the proteoglycan. Through DNA sequencing studies, knowledge of the proteoglycan protein core primary structure will soon be complete. Thus the essential information for proper interpretation of cross-linking experiments as proposed here is available. This approach should reveal, at the molecular level, the nature of many interactions with the proteoglycan aggregate. A rational basis will be provided for subsequent studies of, presumably proteolytic, proteoglycan aggregate degradation which accompanies mineralization. Further cross-linking work may give clear indications of associations of proteoglycan aggregates with other extracellular matrix components and thus an overall view of cartilage organization. Keratan sulfates are constituents of cartilage and bone. they are heterogenous and polydisperse. We propose to determine whether there are discrete differences between keratan sulfate chains from different tissue sources or attached at different sites on the proteoglycan core, as a prelude to investigating the roles of this glycosaminoglycan. At present, it's an open question whether some keratan sulfate chains participate in specific interactions associated with collagen fibrillogenesis or rather serve to inhibit non-specific interactions with proteoglycans.